Stroke is the third leading cause of death in the United States. Despite its prevalence, current treatment options are limited and surviving stroke is still associated with serious morbidity issues. The most recent therapy for ischemic stroke, Alteplase, was approved by the FDA over a decade ago and has serious limitations due to the potential for inducing bleeding complications if administered more than 3 hours after the acute event, and its use is counter-indicated for hemorrhagic strokes. Even so, clinical studies suggest that the combination of this drug with subsequent anti-thrombotic treatment such as aspirin, improves patient outcome. However, such agents can not be used concurrently with tPA because of their potential to exacerbate bleeding despite the known role platelets play in the downstream events triggered by the initial ischemic event. The approach described in this application is to develop a therapeutic antibody directed against a novel target for stroke. Not only does the -platelet GPIba interaction provide a promising target to develop anti-thrombotics with a reduced potential for bleeding complications, but this interaction also appears to play a major role in the secondary thrombosis associated with inflammatory endothelial responses during reperfusion injury. A successful outcome of the research described in this Phase I project, coupled with the research planned for Phase II, would allow us to develop proof of concept and completion of toxicology studies for a promising new therapeutic agent for the treatment of ischemic stroke. PUBLIC HEALTH RELAVANCE: Stroke is the third leading cause of death in the United States. Despite its prevalence, current treatment options are limited and surviving stroke is still associated with serious morbidity issues. The most recently approved therapy (drug) for ischemic stroke, Acteplase, was approved by the FDA over a decade ago and has serious limitations because of its potential for inducing bleeding complications if administered more than 3 hours after the stroke has occurred, which greatly limits its use. If successful, the research we are proposing could lead to a new drug to more effectively treat ischemic stroke. [unreadable] [unreadable] [unreadable]